Tropical forest loss jeopardizes discovery of new drugs

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Ethnobiologists explore the world's shrinking tropical forests

Forests – not big pharma – seem to hold the key on antibiotics

Putting the "ant" into antibiotics

It has been known that deforestation is contributing to global warming for decades, but the effect it’s having on discovering new drugs has been less explored. Tropical forest plants and animals could be a source of new antibiotics to replace the current failing stock, scientists in the field believe.

A recent World Health Organization report shows there is a serious lack of new antibiotics in the pipeline to combat the threat of antibiotic resistance. Globally 700,000 people die every year because of antibiotic resistance, and by 2050 this is expected to rise to 10 million, according to a report by The Review on Antimicrobial Resistance.

After the so called ‘golden age’ of antibiotic discovery in the 1940’s and 50’s, scientists began rediscovering the same antibiotics from the group of soil microbes, Actinomycetes, they had used that proved so successful, so moved on to new methods by creating chemical compounds in a lab. However, billions of dollars later, that didn’t breed the results pharmaceutical companies had hoped for. So many of them abandoned work on new drugs in favor of the guaranteed profitability of improving existing ones. But latterly a combination of over-prescription, people not finishing their course of antibiotics, which leads to antibiotic resistant bacteria, and lack of new drug discoveries has caused a rise in antibiotic resistance. This has prompted a renewed interest in deriving new drugs from natural products, often from largely untapped environments.

One such environment is tropical forests. They cover less than 7 percent of the Earth’s surface yet are home to approximately 50 percent of all land animal and plant species. However, with more than 80,000 acres of tropical rainforest and 135 species of plants and animals being lost daily, extracting drugs from this biome in the near future could no longer be possible.

Cassandra Quave, an ethnobotanist [scientist working on drugs derived from plants] says: “You have mega corporations just destroying these forests, [while] scientists like myself have great difficulty in even accessing these biological resources to study them before they’re gone.”

Drugs used to treat malaria, cancer and glaucoma all originally came from tropical forests and around 120 prescription drugs [this link needs to be more specific] sold globally originate from rainforest plants. And 40 percent of anticancer drugs available between 1940 and 2002 were from natural or naturally derived products.

Partly because of deforestation, current extinction rates are 100-1,000 times higher than natural background rates and as many as 15,000 medicinal plants are under threat. Just of the plant species we know of 70,000 are known to be medicinal, let alone other harboring potential uses such as a material or food. Predictions vary, but only 1 – 15 percent of plant species have been screened for their medicinal potential.

The difficult part is finding the drugs from the many plants. For every 10,000 compounds screened for medicinal properties, about 250 make it to clinical trials, according to Milken Institute Review. Of those only onewill eventually become an approved drug.

Ethnobotanists fight back

Cassandra Quave is an ethnobotanist – someone who studies plants and their practical uses, using indigenous people’s traditional knowledge – something she describes as a “lost art.”

Quave leads an antibiotic drug discovery research team at Emory University, Atlanta, Georgia. The Quave Research Group are looking for what is called ‘antibiotic potentiators.’ They can be used to take antibiotics that no longer work due to bacterial resistance and restore their effectiveness. Her team are looking for treatments for super fungus Candida Auris, which is resistant to many drugs, and undiscovered chemicals that interfere with bacterial signalling, which is is key to bacteria’s ability to produce damaging toxins. Quave also wants to draw attention to curing fungal infections as she says there are few chemical classes that currently treat them.

Cassandra Quave in lab (CC BY SA 3.0)

The team she leads is rare in that it extracts chemical compounds from plants traditionally used as medicines in order to produce drugs. Most pharmaceutical labs now make the chemical compounds drugs derive from synthetically. In the chemistry lab, her team now has around 1,200 extracts from more than 400 different species they have collected.

The plants shipped in to the university come from the south-east U.S. – states like Georgia and Florida – and countries in the Mediterranean basin and Balkans, including Italy, Albania and Lebanon. However, Quave still gets out in the field. This summer she was out with students working on the Aeolian islands, off the coast of Sicily, because of the islands’ remoteness and endemic species.

While the Mediterranean Basin is a ‘hotspot‘ of biodiversity, containing roughly 13,000 endemic species, Quave says she would like to be able to study plants from tropical forests too, but that it’s very difficult to get permits to take plant samples from countries in this environment. She says “I think that there are lots of plants in tropical forests that have not yet been investigated, and we’re facing an alarming grade of deforestation in tropical forests, due to mining, logging and gold and natural resource extraction that’s just destroying large tracks of land … tropical forests are definitely one of those high risk areas where we are rapidly losing those resources for drug discovery.”

She is also concerned by the loss of memory from tribes who have used medicinal plants for thousands of years. “We use that lens of culture also in our drug discovery efforts” and “knowledge of how those [plants] have been used over centuries for food and medicine, and survival,” she says. “It is important to highlight the need to record these things [plants], and help preserve these areas, and create safe havens for these people before it’s all gone.”

He works with Acromyrmex echinatior leafcutter ants collected in Gamboa, Panama. They gather leaves in the rainforest and feed them to a fungus known as Leucoagaricus gongylophorus, which in return supplies them with food. Antibiotic-producing bacteria which live on the ants, known as actinomyces, are the raw material for 60 percent of known antibiotics. The ants feed the bacteria living on them through specialized glands in their exoskeletons and use the antibiotics produced by these bacteria to kill off other microbes that would otherwise infect their fungus garden. If the ants smell infected parts of the fungus they remove it, dump it away from the nest and use anti fungal antibiotics on it to sterilize it. Ant species that farm fungi (Attini ants) have most likely been using antibiotics for more than 50 million years to protect these fungus gardens from pests.

The team Hutchings leads is isolating bacteria from the ants, and seeing if the antibiotics they produce prevents other harmful bacteria from growing. He says the team have identified antibiotics which could be very powerful against ‘superbugs’ like MRSA.

And while Hutchings says only 10 percent of the antibiotics that are made by actinomyces have been discovered, leaving huge room for potential, he says the problem boils down to finances. “Who wants to invest billions of dollars to find new antibiotics? Drug companies don’t want to pay for it. Governments can’t afford to pay for it. Antibiotics don’t make any money, basically.”

Hutchings says “the antibiotics we have are fantastic, but we’ve just used them so badly – they’ve just been giving them out like Smarties, which is the worst thing you can do.” He hopes “we’ve learned our lesson so when we develop a new generation of antibiotics, they’ll be used very carefully.”

London’s Science Museum is hosting a free exhibition on the increasing problem of antibiotic resistant bacteria, ‘Superbugs: The Fight for Our Lives’, which runs until Spring 2019.

Its curator, Sheldon Paquin, told Wikitribune, “this is one of these scenarios where millions of people could die, and are dying, and we could do something about it right now in order to protect people years down the line – if we act. But otherwise, we could very well be part of that statistic where in 2050 we’re looking at 10 million people dying every year from antibiotic resistant infections.”

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